蔣 濤，馮家龍，劉中洪，冉春雷，張杰智，譚 春

低分子肝素預(yù)防幕上高血壓腦出血術(shù)后下肢深靜脈血栓形成的效果觀察

蔣 濤，馮家龍，劉中洪，冉春雷，張杰智，譚 春

目的 評(píng)價(jià)高血壓腦出血術(shù)后使用低分子肝素預(yù)防下肢深靜脈血栓形成的效果。方法 選擇符合條件的82例高血壓腦出血術(shù)后患者分為預(yù)防組和對(duì)照組。預(yù)防組42例，術(shù)后第3天預(yù)防性皮下注射低分子肝素鈣，1次/d，連續(xù)使用14 d，同時(shí)每日行間隙氣壓治療。對(duì)照組40例，僅行間隙氣壓治療，未行抗凝治療。術(shù)前2組均行血漿D-二聚體檢測(cè)，術(shù)后7、14、21 d行D-二聚體檢測(cè)及雙下肢靜脈超聲檢查。結(jié)果 預(yù)防組發(fā)生下肢深靜脈血栓1例(2.38%)，顱內(nèi)出血1例(2.38%)。對(duì)照組發(fā)生下肢深靜脈血栓9例(22.50%)，肺栓塞1例(2.50%)，顱內(nèi)出血1例(2.50%)。兩組間的再出血及肺栓塞發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義，而下肢深靜脈血栓形成差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。兩組間血漿D-二聚體對(duì)比，術(shù)前、術(shù)后21 d差異無(wú)統(tǒng)計(jì)學(xué)意義，術(shù)后7 d、14 d差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論 高血壓腦出血術(shù)后患者使用小劑量低分子肝素預(yù)防下肢深靜脈血栓形成安全有效，應(yīng)積極推廣。

下肢深靜脈血栓；腦出血；低分子肝素

高血壓腦出血，又稱出血性腦卒中，是一種病死率和致殘率均很高的急性腦血管病，占所有卒中的10%～30%[1,2]。該病是基層醫(yī)院最常見的病種之一，對(duì)于出血量大的患者往往需采取手術(shù)治療。雖然隨著微創(chuàng)、顯微技術(shù)被廣泛應(yīng)用及治療手段的逐漸增多，病死率、致殘率有所下降，但術(shù)后仍有一些并發(fā)癥困擾著醫(yī)務(wù)人員。下肢深靜脈血栓(deep vein thrombosis of lower extremity, LDVT)就是腦出血患者常見并發(fā)癥之一，如果治療不及時(shí)易繼發(fā)致命性肺栓塞，嚴(yán)重影響預(yù)后。對(duì)此，筆者采用低分子肝素結(jié)合間隙氣壓治療和預(yù)防高血壓腦出血術(shù)后LDVT形成，效果較好。

1 對(duì)象與方法

1.1 對(duì)象 選擇我院神經(jīng)外科2009-01至2013-06幕上高血壓腦出血手術(shù)患者。納入標(biāo)準(zhǔn)：(1)有突發(fā)頭痛、嘔吐、偏癱、失語(yǔ)、意識(shí)障礙等臨床表現(xiàn)；(2)頭顱CT證實(shí)腦實(shí)質(zhì)內(nèi)出血；(3)均行開顱血腫清除術(shù)或顱內(nèi)血腫碎吸術(shù)。排除標(biāo)準(zhǔn)：(1)既往無(wú)高血壓病史；(2)發(fā)病后存活時(shí)間少于3周(死于肺栓塞的除外)；(3)深靜脈血栓病史；(4)血小板計(jì)數(shù)<100×109/L；(5)證實(shí)有血管畸形或動(dòng)脈瘤等腦血管性疾病導(dǎo)致者；(6)對(duì)肝素過(guò)敏者。符合上述條件的有82例，其中基底節(jié)區(qū)出血52例，丘腦出血15例，原發(fā)性腦室出血9例，腦葉出血6例。按隨機(jī)數(shù)字表分為預(yù)防組(n=42)和對(duì)照組(n=40)，預(yù)防組簽署使用低分子肝素知情同意書。兩組的一般資料和GCS評(píng)分比較，差別無(wú)統(tǒng)計(jì)學(xué)意義(表1)。

表1 兩組高血壓幕上腦出血患者的一般資料和GCS評(píng)分 ±s)

注：預(yù)防組采用使用低分子肝素，對(duì)照組僅采用常規(guī)治療和間隙氣壓治療

1.2 方法 預(yù)防組常規(guī)脫水、止血、對(duì)癥、改善腦功能、營(yíng)養(yǎng)支持、防治并發(fā)癥及間隙氣壓治療，于手術(shù)后第3天預(yù)防性皮下注射低分子肝素鈣4100 U，1次/d，連續(xù)用14 d。對(duì)照組予常規(guī)治療和間隙氣壓治療，不注射低分子肝素鈣。

1.3 DVT診斷 兩組均于術(shù)后7、14、21 d，根據(jù)Wells評(píng)分標(biāo)準(zhǔn)[3]，進(jìn)行Wells評(píng)分，若評(píng)分中低度者，則于當(dāng)日行雙下肢靜脈超聲檢查，若為高度者，且下肢超聲檢查陰性，則需行MRI靜脈成像或靜脈造影明確。超聲診斷 LDVT標(biāo)準(zhǔn)： (1)靜脈腔內(nèi)強(qiáng)弱不等的實(shí)性回聲；(2)加壓管腔不變癟或部分變癟；(3)脈沖和彩色多普勒在病變處不能探及血流或顯示血流充盈缺損。

1.4 D-二聚體檢測(cè) 試劑為西門子醫(yī)療診斷公司生產(chǎn)的D-二聚體試劑盒，采用免疫比濁法測(cè)定。術(shù)前兩組均行血漿D-二聚體檢測(cè)，術(shù)后7、14、21 d復(fù)查D-二聚體。

2 結(jié) 果

預(yù)防組發(fā)生LDVT僅1例，無(wú)肺栓塞病例；對(duì)照組發(fā)生LDVT 9例,肺栓塞1例(術(shù)后16 d死亡)；兩組間的再出血、消化道出血及肺栓塞發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義，而LDVT發(fā)生率差異有統(tǒng)計(jì)學(xué)意義(P<0.05，表2)。兩組間血漿D-二聚體對(duì)比，術(shù)前、術(shù)后21 d差異無(wú)統(tǒng)計(jì)學(xué)意義，術(shù)后7 d、14 d間差異有統(tǒng)計(jì)學(xué)意義(P<0.05，表3)。

表2 兩組高血壓幕上腦出血患者發(fā)生LDVT及其他并發(fā)癥的情況 (n；%)

注：預(yù)防組使用低分子肝素，對(duì)照組僅采用常規(guī)治療和間隙氣壓治療；LDVT指下肢深靜脈血栓

表3 兩組高血壓幕上腦出血患者手術(shù)前后D-二聚體檢測(cè)情況 ；mg/L)

注：預(yù)防組使用低分子肝素，對(duì)照組僅采用常規(guī)治療和間隙氣壓治療

3 討 論

腦出血患者發(fā)生血栓栓塞性疾病的風(fēng)險(xiǎn)很高[4,5]。近年來(lái)，廣泛采用多普勒超聲和MRI等診斷方法，深靜脈血栓的檢出率為17%～40%[6，7]，常見于出血后2周內(nèi)[8]。高血壓腦出血術(shù)后患者易出現(xiàn)LDVT主要有以下幾個(gè)原因：(1)術(shù)后長(zhǎng)期臥床，下肢的血液失去肌肉泵的擠壓作用，血流緩慢，在下肢靜脈竇形成渦流，易激活內(nèi)源性凝血系統(tǒng)，致使血栓形成；(2)多為老年人，自身血管條件不好，且輸液時(shí)間長(zhǎng)，經(jīng)常需使用股靜脈穿刺輸液，從而直接導(dǎo)致下肢靜脈壁機(jī)械性和化學(xué)性損傷；(3)因廣泛使用脫水藥，導(dǎo)致靜脈淤滯、血液濃縮，且輸甘露醇、脂肪乳等液體，易損傷血管；(4)術(shù)后常規(guī)應(yīng)用止血和抑制纖溶的藥物，使血液處于高凝狀態(tài)。

深靜脈血栓的嚴(yán)重并發(fā)癥是肺栓塞，這是深靜脈血栓最兇險(xiǎn)的并發(fā)癥，雖然臨床發(fā)生率不高，但病死率卻極高。英國(guó)牛津郡社區(qū)卒中項(xiàng)目(Oxfordshire community stroke project, OCSP)顯示，5%的腦出血患者在發(fā)病30 d內(nèi)死于致死性肺栓塞[9]。

D-二聚體是纖維蛋白單體經(jīng)活化因子交聯(lián)后，再經(jīng)纖溶酶水解作用后的一種特異性降解產(chǎn)物，其水平增高反映凝血和纖溶系統(tǒng)被激活。深靜脈血栓形成后由于激發(fā)纖溶活性亢進(jìn)，D-二聚體水平明顯升高，同時(shí)腦出血病情越重，GCS評(píng)分越低，D-二聚體含量也越高[10]。兩組術(shù)前D-二聚體水平無(wú)明顯差異，術(shù)后7 d、14 d預(yù)防組明顯低于對(duì)照組，顯示低分子肝素鈣可能是通過(guò)降低D-二聚體水平來(lái)緩解高血壓腦出血患者術(shù)后高凝狀態(tài)。術(shù)后21 d兩組無(wú)差別，可能由于腦出血7～10 d為L(zhǎng)DVT高發(fā)期，到21 d時(shí)已過(guò)高發(fā)期，體內(nèi)繼發(fā)性纖溶活性逐漸恢復(fù)正常。

低分子肝素由普通肝素通過(guò)解聚而成，具有快速和持久的抗血栓形成作用，生物利用度高、血漿半衰期長(zhǎng)、出血傾向較低、使用簡(jiǎn)單以及不必常規(guī)監(jiān)測(cè)等優(yōu)點(diǎn)[11]。在國(guó)外，臨床醫(yī)師非常重視腦出血住院患者的深靜脈血栓和肺栓塞的預(yù)防，推薦在彈力襪基礎(chǔ)上使用間歇性空氣壓縮裝置，同時(shí)建議在證實(shí)出血停止之后，臥床患者在發(fā)病1～4 d后可考慮皮下注射小劑量低分子肝素或普通肝素以預(yù)防靜脈血栓栓塞[12]。但有人指出，應(yīng)用肝素預(yù)防深靜脈血栓的同時(shí)，也可增加出血并發(fā)癥的危險(xiǎn)[13]。本研究發(fā)現(xiàn)，預(yù)防組發(fā)生下肢深靜脈血栓僅1例，發(fā)生顱內(nèi)出血1例，而對(duì)照組為9例，預(yù)防組LDVT發(fā)生率明顯下降，且未明顯增加再出血和消化道出血的發(fā)生。因此筆者認(rèn)為，采用小劑量低分子肝素結(jié)合間隙氣壓治療和預(yù)防高血壓腦出血術(shù)后LDVT形成效果較好且較安全。

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(2014-06-05收稿 2014-07-18修回)

(責(zé)任編輯 武建虎)

Low dose of low molecular weight heparin for prevention of lower extremity deep vein thrombosis after hypertensive intracerebral hemorrhage operation

JIANG Tao，F(xiàn)ENG Jialong，LIU Zhonghong，RAN Chunlei, ZHANG Jiezhi，and TAN Chun.

Department of Neurosurgery, Chongqing Municipal Corps Hospital，Chinese People’s Armed Police Forces, Chongqing 400061, China

Objective To evaluate the outcome of low molecular weight heparin (LMWH) for the prevention of lower extremity deep vein thromboembolism (LDVT) in patients with hypertensive intracerebral hemorrhage after operation. Methods 82 patients with hypertensive intracerebral hemorrhage after operation were divided into two groups: prothylactic group (n=42) and control group (n=40). The patients in prothylactic group were injected hypodermically with LMWH from day 3 to day 14 after operation and treated with intermittent pneumatic compression from 1 to 21 days continuously. Whereas the patients in control group were treated only by intermittent pneumatic compression. The plasma D-dimer (D-D) was measured in all patients before operation and was determined at day 7, 14, 21 after operation. The deep veins of lower limbs in all patients were examined with colour Doppler at day 7, 14, 21 after operation to observe venous thromboembolism. Results Only one case of deep vein thrombosis in prothylactic group(2.38%), and one cerebral hemorrhage(2.38%)recurred. In control group, deep vein thrombosis was found in 9 cases(22.50%), and one cerebral hemorrhage(2.50%) recurred, and one pulmonary embolism(2.50%)was found. The DVT incidence between two groups was significantly different(P<0.05), but the PTE incidence was not significantly different. D-D content at days 7, 14 after operation in control group was significantly higher than that in prophylactic group (P<0.05), but the D-D level had no significant difference before operation and at day 21 after operation between the two groups. Conclusions LMWH is safe and effective for the prevention of LDVT in patients after hypertensive intracerebral hemorrhage operation.

deep vein thrombosis of lower extremity；intracerebral hemorrhage；low molecular weight heparin

蔣 濤，碩士，主治醫(yī)師，E-mail：1048197834@qq.com

400061，武警重慶總隊(duì)醫(yī)院神經(jīng)外科

馮家龍，E-mail：wjyysjwkxwk@sina.com

R651.1